Desiccation



May 16, 1950 E. W. FLOSDORF ETAL DESICCATION a Sheets-Sheet 1 Original Filed Feb. 8, 1940 E. W. FLOSDORF ETAL DESI CCATION May 16, 1950 3 Sheets-Sheet 3 Original Filed Feb. 8, 1940 W Wm @M w% Z. WOW

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Patented May 16, 1950 DESICCATION Earl W. Flosdorf, Forest Grove, and Francis Jo- 'seph Stokes, .lr rhiladelphia, Pa., assignorsto Tabor Olney Corporation, Baltimore, Md.,

a corporation of Maryland Original application February 8, 1940, Serial No.

This invention relates to methods of and apparatus for improving the keeping qualities of liquid-containing biological substances including fruit juices, vegetable products, protein solutions, normal and immune blood serum, bacterial cultures, viruses and other labile biological and be used, only the addition of water thereto, in

an amount corresponding to the normalwater content is necessary to restore the preserved material to its original condition; or by the use of a lesser amount of water a more concentrated product can be obtained.

It has long been known to heat materials to eilect the evaporation of the water therefrom. This procedure, however, is usually accompanied by deleterious eiiects when applied to the treatment of biological materials since the evaporation of the water produces a concentrating effect causing breakage of the tissues and cells and allows chemical alteration of the complex constituents, thereby so completely changing the structure as to permanently alter the very qualities which are sought to be preserved.

It has more recently been established that if, prior to the removal of the water from the material, the solid constituents can be locked in position, thereafter the removal of the water can be eii'ected without injury to the biological material. To this end it has been proposed to freeze the biologically active substances and thereafter to effect the removal of ice by sublimation. It has also been found that the water vapor removed from the material by sublimation need not be condensed in the manner of a complete sublimation cycle, but thatsuch water can be absorbed by a suitable chemical desiccant if Divided and this application Septem ber 19, 1946, Serial No. 698,076

3 Claims. (Cl. 99-199) found that either a rapid freezing by indirect heat exchange or a vacuum freezing can be employed with good results insofar as avoiding injury to the product is concerned.

Irrespective of the freezing process used or the manner of collecting the sublimed water vapor, it has been established that the broad concept of freezing and removing the ice, in the form of a vapor, produces results far superior to those attainable from heat treatments since no concentration of solute occurs during the process itself and furthermore the freezing temperatures employed avoid chemical interactions. Thus the desirable qualities of biological materials are retained unimpaired over long periods of storage so that the product with pure water added thereto may be used interchangeably with the original product.

Although the practice of the processes of the prior art. involving the freezing of the liquidcontaining biological materials and the sublimation of the ice therefrom are satisfactory in that the dehydration treatment is not injurious to the material treated, the prior processes are not as satisfactory as they otherwise might be because the water content of the material after treatment is very seldom uniformly below or 1 percent by weight. The keeping qualities of the product are directly proportional to the extent of dehydration so that a water content 0! /2 or 1 percent is undesirable when the product is to be stored for extended periods of time.

It has been customary to expose the surface of the containers in which the material is treated directly to the outside atmosphere so that a source of heat for the sublimation may be available when the material is subjected to high vacuum. This expedient, however, presents a diiiiculty when the material to be treated is frozen by a process involving a degassing and a high vacuum step. This'is because the presence of heat from the surrounding atmosphere, so readily available by conduction through the walls of the containers to the material therein adjacent such walls, produces considerable evaporation of the material before freezing, which evaporation is made evident in the final product by a particularly heavy skin over the surface of the dry me.-

terial. Also unless an elaborate system of controls is provided for regulating the temperature 3 of the atmosphere in a changing fashion, the liability of melting or softening of the materials being dried, irrespective of the manner of freezing, is very great and constitutes a serious hazard to successful drying of valuable products.

According to this invention it ispossible to dehydrate biologically active materials to a water content of less than .050 percent in a relatively short period of time while producing a product characterized by the absence of the heretofore known heavy skin over the surface of the dry material. This object is obtainable primarily because, according to the teachings of the present invention. the latent heat of sublimation is supplied, not at random by conduction through the walls of the container, but in a completely controlled manner which control is automatically responsive to the rate of sublimation. To this end this invention contemplates a process wherein the liquid-containing biological substance is froun and the ice so produced is sublimed while the vapors evolved are concomitantly absorbed in the chemical desiccant, which absorptive reaction results in the evolution of heat. The heat of the absorption is used as the source of heat for the sublimation and by constantly transferring such heat from the desiccant to the treated material, the former is kept cool and consequently its aqueous tension properly low so as the keep it at maximum efilciency.

It is a further object of the present invention to provide an apparatus wherein the foregoing process may be advantageously accomplished and wherein the desiccant and biological material may be placed in heatexchange relationship while at the same time the flow of vapors between the biological material and the desiccant is entirely unrestricted as distinguished from the small diameter conduits heretofore known to the art. By this expedient, the structure of the apparatm is tremendously simplified and the control of the sublimation much more readily eifected. Furthermore, by the use of a single chamber without pipe lines extending between the desiccant and the-biological material. leaks destructive of high vacuums, which were undesirable incidents to the use of prior apparatus, are avoided. By the use of the apparatus of the present invention the desiccant may be regenerated in situ in such a manner that the regenerative step will alsoproduce the complete sterilimtion of the entire apparatus. With the apparatus of the present invention it is also possible to remove the material from the apparatus after treatment in a manner to prevent contamination thereof by moisture or micro-organkms.

By the use of this process and apparatus, it is possible to treat liquid-containing biologically active materials and thelike in large or small quantities and either in treatment or in final storage and/or final shipment containers. It will be imderstood of course that in the case ofserumstheflnalcontainerwillbeusedas an ordinary practice since a minimum of handling is desirable.

The process of the present invention contemplats the freezing of the liquid-containing biological materials. either by indirect heat exchange with a cooling material or by degasing followed by subjection to a high vacuum. In either case the materials are maintained in a zone isolated from the atmosphere insofar as pressure and heat exchange are concerned. The frozen material is dehydrated by subliming the ice contained therein while concomitantly absorbing the vapor in a chemical desiccant. which desiccant is so positioned with respect to the material undergoing treatment as to permit of heat exchange between the desiccant and the material. By this expedient, heat control is effected both automatically and withv a high degree of eiiicienc'y. As the vapor is withdrawn from the material undergoing treatment,,it is absorbed by the desiccant. It is well known that absorptions are generally exothermic in" character, while sublimation is endothermic. Consequently, heat is required at'the point where sublimation is taking place while heat is supplied to meet that requirement at the point of absorption. Since the absorption cannot occur except as the vapor is supplied to be absorbed, it will be seen that an automatic heat supply is provided. Conversely, the desiccant will be kept cool because of the fact that the .heat incident to the absorption is radiated through the high vacuum to the sublimation reaction but at a rate automatically maintained at a point not high enough to permit thawing yet suiliciently high to produce as rapid a sublimation as is possible when the escaping vapors are unrestricted in their movement. Because of the facts that the desiccant is kept cool and consequently its aqueous tension is maintained at a low point, very emcient desiccation results.

While the process outlined-above is wholly automatic and very satisfactory as long as the desiccant employed is at high absorptive emciency, after portions of the desiccant have become saturated it has been found desirable to provide a heat source to augment the heat of absorption. This supplemental heat source is so controlled that it is brought into play only when the heat of absorption in those portions of the desiccant body directly. responsible for the delivery of heat to the material being treated falls below that required for eflicient operation. Such a heat source will permit the use of all portions of the desiccant until saturation of the total body is approached while temperature control derived from the'desiccant is maintained. By the provision of this means to augment the heat supply it is possible to employthe desiccant for a longerperiod of time before regeneration is necessary.

The advantages of the present process may be more fully appreciated from a consideration ofthe following specific example wherein 4100 mi]. of human blood serum and milk were simultaneously treated in a heat insulated reaction zone. 900 pounds of calcium sulfate were placed in heat exchange relationship with the material to be treated.- Thereafter the reaction zone was degassed for a period of 90 minutes under lowvacuum, approximately 10 mm. mercury absolute. At the end of the degassing period the temperature of the calcium sulfate had risen from an initial temperature of 37 C to 57 C. The material was then frozen by subjecting it to high vacuum of .160 to .400 mm. of mercury absolute and this vacuum was maintained for a period of 47 hours. During the degassing period the highest temperature reached by the desiccant was 57 C. which was minutes after the process had been started. .75 minutes later, however, the temperature had been lowered to 31 C. and even at the end of the 47-hour treatment the desiccant temperature was only 33 C.

Following subjection of the material to this treatment for 47 hours, two lo-milliliter samples was characterized by the absence of the thick skin which had been an undesirable characteristic of material treated according to the previously known processes.

Serum of guinea pigs dehydrated according to the present invention having a water content of .050 percent or less may be uniformly maintained with unaltered complementary activity under ordinary refrigeration conditions to 8 C.) for three years and longer, while previously known products having a water content of about .5 percent or more by weight can be uniformly kept under the same conditions without loss of complementary activity not longer than thirteen months.

In the case of citrus fruit juices, it is generally advisable to dehydrate in a vessel other than that in which the final product is to be marketed. But the tendency of the dried material to absorb water renders it necessary to practice a special technique with these materials. It has been determined that the'oils and other substances obtained by dehydration of citrus fruit juices, such as orange juice, are exceedingly hygroscopic and that the presence of relatively small amounts of water gives the material a melting point in the neighborhood of normal room temperature. Fu-

sion of the particulate product, which is read ily soluble in water, gives asolid compact cake dissolving in water only with great difficulty. However,' when orange juice is dehydrated to an extremely low moisture content, the oil in the separate particles does not soften sufficiently to cause the particles to stick together.

Citrus products cannot be dried in their final containers on a practicable scale and therefore transferring of bulk-dried material to the final individual market containers is necessary, such transferring needing to be done with the complete exclusion of moisture. Furthermore, the market containers themselves, prior to filling, must be treated to remove the minute amounts of moisture which normally are present on the surface of any material which has been exposed to the atmosphere, and in the seams of containers, such as tin cans. The said moisture may he removed by heating, by desiccation, or in any other suitable manner.

Complete exclusion of moisture from the packaged product requires that even momentary contact with the atmosphere be avoided, five seconds being sufficient to permit the absorption and re-= tention of sufficient water to cause fusion of the particles because of the extremely hygroscopic nature of the juice when dried to a very low'rnoisture content. The product is normally intended to be stored for days and weeks at room temperature and deterioration due to the particles um within the Cryochem apparatus with dry air or inert gas in the usual fashion. The pans in which the juice is placed for desiccation are fitted with lids which can be snapped closed within the chamber and then these can be carried to and placed within the can filling and sealing equiplies gasket M.

ment. The latter equipment is readily enough arranged for complete exclusion of moisture.

While perfection in transferring the dried juice is practically impossible to attain, it has been found that juices dried to a moisture content.

of 0.05% and which do not have a final moisture content substantially in excess of 0.15% as packaged may be obtained in the above manner. These retain the desirable properties of a particulate product over very long periods of time.

Other objects and advantages of the present invention will be apparent from a consideration of the following detailed description when taken in conjunction with the annexed drawings wherein an apparatus constructed according to the present invention;

Figure 2 is a vertical sectional view taken along the line 22 of Figure 1;

Figure 3 is a view in section taken along the line 33 of Figure 2;

Figure 4 is a fragmentary view in section taken along the line 4-4 of Figure 2;

Figure 5 isa-vertical sectional view taken along the line 5-5 of Figure 1;

Figure 6 is a fragmentary partially in section view of a sterility rack for supporting containers in the treatment zone;

Figure 7 is a fragmentary view in elevation of a sterility rack showing several containers depending therefrom; and

Figure 8 is a detail view of the auxiliary means for effecting a seal between the reaction vessel and the cover therefor.

Referring in detail to the drawings, I0 designates a vacuum chamber in which the process of the present invention may be advantageously carried out. This chamber is reinforced against pressure incident to the withdrawal of air therefrom and is provided with a heat insulating sheath H. Chamber i0 is also provided with a cover l2 which may be locked vapor-tight.

Around the open end of container Hi there is attached a ring I3, L-shaped in cross section, and

functioning as a seat for annular rubber sealing gasket i i which is interposed between the same and cooperating annular flange i5 provided on cover it. Cover 02 is supported by an arm it, one end of which is pivotally attached at l! to the outside wall of container it. Arm it is bent at it? so that the free end thereof may be swung into a position to overlie the vertical axis of com tainer ill. At the point of bend a reinforcing element i9 is provided for the purpose of imparting rigidity to arm it so that it may support cover i2. The free end of arm it is drilled and a screw Ed is passed therethrough, said screw being pro vided with an interiorly threaded handle 21 and an enlarged end 22 which is keyed in socket 23 in the center of cover i2. When cover 92 is to be placed in sealing position to act as a closure for the open end of container 60, it is swung about its pivot point i'i until flange of the cover over- When this position has been reached, handle 2! is turned to increase the effective length of screw 28 between the end of arm l6 and socket 23. This operationwill press fiange 85 of cover i 2 tightly against gasket M to assist in maintaining a vacuum tight seal. When it is desired to remove the cover, handle 25 is moved in the opposite directiorrthus shortening the said effective length of screw 20 to permit the movement of arm I6 and cover i2 about the axis 1 1.

In view of the fact that materials to be treated Figure 1 is a plan view of one embodiment of I provided. The means consist of -a series of threaded studs I4. shown-in detail in Figure 8, pivotally attached to member II and adapted to be swung into position in notches II provided in fiange ll and in'ring It. In this position interiorly threaded nuts I. may be screwed thereon to a point where said nuts press tightly against fiange ll of cover I! thus acting to further compress gasket ll.

Near the base oi .and within container it there is attached to the wall thereof an annular member 21 and two chord-like channel bars ll supported from the bottom of chamber II which act as a supp rt for a series oi desiccant trays 2!. Each of these desiccant trays is provided with a perforated bottom II and solid side walls Si. Alternate trays it are provided with centrally disposed cylindrical chimneys II which are made of the same material as the bottoms ll. At spaced points about the upper rim 0! each tray 2! are projections it which act as supports for the next tray above. The apparatus shown contains ten trays and overlying the topmost tray is a crossshaped spider 34 made of channel bars and positioned so as to rest on projections 33. Centrally disposed on the spider 34 there is a cylindrical rack'tl having a removable cover it provided with handles 37. The side walls oi the rack II are perforated as shown in Figures 6 and 7, the periorations being in staggered rows between each of which an interior annular angle iron 38 is positioned to act as a stop for the free end oi containers it placed therein. Note that the annular angle irons are vertically adjustable by alteration of the position of screw ll so that the angle defined by the container and the cylindrical wall of rack Il may be varied to avoid spilling oi the contents of the container. This is accomplished by moving screws ll vertically in slots ll provided in cylindrical wall II.

In the side wall oi the chamber ll, below the point where the desiccant trays are placed, there is provided an exhaust pipe I! provided with a valve 48. The pipe 42 is connectcd to asuitable pump, not shown, and constitutes the line through which evacuation of the chamber is eiiected. A connection 44 is provided in the upper portion oi' the chamber II. This lineis provided with a valve ll which is vapor-tight when either open or closed. A container ll, similar to containers It. is attached to line 44 so that the reaction therein may be observed by the operator, espe-' ctally when the air is first evacuated from the chamber II as the process is begun. Adjacent connection 44 there is provided a pipe connection 41 leading to the outside atmosphere and subject to being placed in communication therewith by valve ll. When it is desired to relieve the vacuum existing within chamber it, the valve I may be opened so that air may pass through the pipe line 41. Within the line there is provided a filter ll of cotton or other suitable material and a desiccant II. It will be seen as air or other gas is admitted to the chamber it will be filtered and dehydrated in passage.

Mounted adjacent primary chamber it there is an auxiliary chamber ll connected to the former through air ducts [I and I3. Chamber ll consists of a hood I, side walls II and a bottom or base portion It defining an interior chamber. Surrounding the primary side walls ll and spaced therefrom are additional walls I! serving to de-. fine a space completely surrounding the interior 1 alter. the spider 34 carrying the sterility rack 8" 8 chamber. Connections for a fiuid duct, not shown.

'areprovidedattla. Bindinlmllluitlbll shleldedinboxll are attachedtoandinsulated iromanupperportionotsidewalllloi'theintariorchamber. Alsoattachedtothhwallars-a series 01' transverse supports 0i havingreaistanoo elements It depending therefrom. (hrrrent h suppliedtothe resistance elementsthroughbindingpostsllandsupportstli'romlead-in wiresllb.

Intermediatechambers II and llareslidevalvea 'a which may be closed vacuum-tight to isolate chamber II from chamber II or opened to place the two chambers in communication. In order toeil'ect a circulation oi air between said'two chambers, a fan 04 is provided. driven iron: a motor I in a direction such that air is'iorced downwardly through the chamber Ii. The ian motor assembly is supported on a bracket is extending from the side wall of chamber ll.

When air is circulated through ducts II and It, and consequently through chambers II and Ii, heat is imparted to the air, or regeneratim or the desiccant and sterilization of the apparatus, by closing .the circuit including lead-in wires llb. In order to effect automatic temperature control during this heating operation; a thermostat BI is mounted near the bottom oi chamber II and is connected by suitable electric conduits to act as a secondary circuit breaker as regards the circuit supplying current to resistance elements ll.

While it will be recognized that during the conduct oi the desiccative stage of the process of the present invention in the apparatus now under. consideration, temperature control will be efiected automatically by the absorption of water in the desiccant placed in trays 2!. In the event an auxiliary heat source-is needed. such heat may be supplied automatically from an electric light bulb l'l attached to the top It of supporting rack II. This bulb is supplied through suitable conduits passing through the side wall of chamber II. The circuit may be closed by primary circuit breaker it or through the action of thermostat I. which is placed in the top desiccant tray. In this way the automatic supply of auxiliary heat is closely co-ordinated with the automatic supply from the heat of reaction of water vapor with the momentarily closing the circuit supplying bull) I! by operating push-button ll while lookirl through sight glass H which is mounted in the.

top I2 01' the chamber II.

The temperature of the desiccant at all timq is rendered observable by the provision of our mometer 12 mounted in the top desiccant tray. At the base of chamber ll another thermometer It is mounted for rendering observable the temperature oi air passing through the duct II, from resistance elements 82 in chamber ll, during regeneration and sterilization.

When the process is carried out according to the present invention, employing the apparatus just described, it is necessary to place a desiccant within the trays 29 in the position shown in the drawings. Desiccant II is also placed in the pipe line 41 as well as the filtering material ll. Therethe desiccant. In order to effect this step, valves 83 are opened and the circuit supplying resistance elements 62 is closed, the thermostat being I set to a suitable temperature, approximately 375 I"., when calcium sulfate is used as the desiccant.

The fan 64 is then started and will effect the circulation of air through the heat exchanger and the chamber In in the direction of the arrows in Figure 2. This temperature is maintained until the entire apparatus. has reached at least 300 1''. in order to effect complete sterility. Thereafter the circuit supplying resistance element 62 is opened and the fan '84 is permitted to continue to run while a cooling material is circulated through-lead-ins 58b and around wall lit to cool the sterile air being circulated in the chamber. When the sterile air and container have been sufficiently cooled so as to lower the aqueous tension of the desiccant, fan 84 is shut I off and valves 63 are closed vacuum-tight. At this point a series of glass containers 39 having ends of reduced diameter are placed within the sterility rack 35 with their open ends in communication with the interior thereof. Cover i2 is then fastened vacuum-tight and the air is slowly evacuated from the chamber through pipe line 42. The valve 43 is opened and regulated in order to control the degree of vacuum. For the first to minutes of operation, the operator regulates this valve so that the gases in the material in the observable container at 48 are not released too rapidly and will not cause the material to splash out through the neck. If conditions in container 46 are satisfactory, the operator will know that similar conditions obtain in containers 39. Furthermore, use may be made of the sight glass if placed in the cover l2 of the chamber to enable the operator to see the condition of the material being processed inside. When all the gases are thus released, the valve 43 is closed tight and the gradual increase in vacuum and the consequent evaporation and cooling effect causes the material in the containers to freeze. Thereafter, a high vacuum is placed on line 42. This high vacuum will effect the sublimation of the ice formed by the freezing of the material in containers 39, the subiimated vapor being absorbed by an exothermic reaction with the chemical desiccant. The heat of this exothermic reaction will be transmitted to containers 39 whereby to supply the latent heat of sublimation. The vacuum is maintained for 6 to 24 hours or longer depending upon the amount of the individual volumes 'in the containers at the end of which timethe material in containers 39 will be dehydrated to an extent approaching .050 percent water con tent or less. At this point the valve 43 is closed chamber i0 to overlie rack 35.

and valve 38 is opened admitting dry sterile air to the chamber. @over 82 may be opened and the containers withdrawn one by one to be sealed in any known manner.

Because of the fact that the air, or other gas such as nitrogen or argon, used to break the vacuum in container i0, is filtered and dehydrated while passing through line 41, the interior of rack 35 will be filled with dry sterile air or gas. Consequently, when containers 39 are removed from the rack they will contain only sterile air or gas and the material treated. The thin neck may be heated and drawn out to a point to seal the container while a plug of cotton or similar material may be placed in the aperture in rack 35 from which the container" was withdrawn. This expedient prevents the ingress of non-sterile-air to the interior of rack 35. In lieu of containers 39 it is possible. to'use bottles, the mouth of which may be plugged in one or more known ways. Asepsis within the container 35 is maintained in the same manner.

It has been found that four or more dehydration runs of the typ lust described may be conducted before it is necessary to regenerate the desiccant contained in trays 29. When regeneration is to be effected,jcover I2 is lowered and fastened. Valves 43, 45 and 48 are closed and valves 63 are opened. The circuit, supplying resistance element 62 is closed and fan 84 is placed in operation. The hot air at the proper temperature is passed as in the original .sterilizatlon step and in addition to sterilizing, effects the regeneration of the desiccant by the removal of water therefrom. After regeneration, cover I! is raised above gasket i4 so that the warm air of high moisture content is removed from chamber iii. The cover is then closed and the air is cooled as in the original sterilization step; It will be noted that the operation just described will effect the sterilization of all of the removable elements in chamber it which include the supports 29, the sterility rack 85 and the various controlling devices. Desiccant 50 will be regenerated at the same time that the primary desiccant is restored.

It will be apparent that any heat exchanger may be substituted in the chamber 5i ano it is proposed to pass hot flue gases through a bank of tubes in order to effect the necessary heating of the air. Water or other fluid jackets may be substituted in the cooling step.

In the event it is desired to effect the freezing of the biologically active materials directly by heat exchange from a cooling medium, refrigeration coils may be mounted at the top of the In such event, the materials are frozen either before or after placing the containers in the chamber iii. In the former case, the refrigeration coils serve merely to prevent thawing of the prefrozen materials during evacuation'of the apparatus to the point where the cooling effect of rapid evaporation will maintain the frozen state. Sublimation, of course, will be effected as before.

In the specification and claims thereof the term sublimation is used to define the change of a solid to a gas without intermediate passage through a liquid stage irrespective of whether i or not the vapor so formed is, thereafter, condensed.

While the desiccant used in the process herein described is specified to be calcium sulfate, any

. porous, non-deliquescent, solid, heat regenerable desiccant may be used.

This application is a division of our prior apcitrus products which comprises freeze-drying a citrus product to a moisture content not substantially in excess of 0.05%, transferring the dried material to and hermetically sealing said material in a container after treating said container .to remove entrapped moisture from the inner walls thereof, and maintaining the moisture absorption during the transferring and sealing operation to an extent such that after seal- 

1. THE PROCESS OF PACKAGING AND PRESERVING CITRUS PRODUCTS WHICH COMPRISESS FREEZE-DRYING A CITRUS PRODUCT TO A MOISTURE CONTENT NOT SUBSTANTIALLY IN EXCESS OF 0.05%, TRANSFERRING THE DRIED MATERIAL TO AND HERMETICALLY SEALING SAID MATERIAL IN A CONTAINER AFTER TREATING SAID CONTAINER TO REMOVE ENTRAPPED MOISTURE FROM THE INNER WALLS THEREOF, AND MAINTAINING THE MOISTURE ABSORPTION DURING THE TRANSFERRING AND SEALING OPERATION TO AN EXTENT SUCH THAT AFTER SEALING IN SAID CONTAINER, THE DRIED MATERIAL HAS A MOISTURE CONTENT NOT SUBSTANTIALLY IN EXCESS OF 0.15%. 